Foundations of Transplant

What does Myeloid Stem Cell include?

Erythroblast → Produce RBCs

Megakaryoblast → Produce platelets

Myeloblast → Produce Eosinophils, Neutrophils, Basophils

Monoblast → Monocyte and macrophage

• First responders to injury (not pathogen specific)

What does Lymphoid Stem Cell include?

B cells

T cells

Natural Killer Cells

• Respond later but pathogen specific

What is the function of thymus?

It is the powerhouse of mature T cell production.

After stem cells leave the marrow, cells destined to become T cells travel to the thymus for maturation.

Which organ is responsible for filtering white cells, platelets and other substances?

Spleen

What is immunosenesence?

The reduction in size of thymus and function of immune cells.

T lymphocytes

• Originates in the thymus

• Mature into T cells

• Contribute to adaptive immunity

• Adaptive immunity - the immune system response to the environment as means of becoming stronger

B lymphocytes

• Originates in the bone marrow

• Mature into B cells

• Contribute to adaptive immunity

Natural Killer Cells

• Presents in the thymus, bone marrow, blood and lymph nodes

• Product of innate immunity

• Innate immunity - automatically regulate and destroy damaged cells without the use of any other organism

What is Histocompatibility?

Refers to how well cells of a donor and a recipient will behave with one another once a transplant has been completed.

Human leukocyte antigen (HLA) matching

• Glycoproteins found on WBCs and almost all cells in the body

• Play essential role in immune defense and allow the immune system to distinguish the body’s cells (self) from tumor cells (non self)

• Markers to determine whether the donor is an appropriate match.

• Also assess exposure to previous infections for which antibodies may be present (CMV, Epstein-Barr virus)

What is Graft-versus-tumor effect?

• Appear after allo transplant

• The graft contain donor T cells which can be beneficial for the recipient by eliminating residual malignant cells.

• Plays a significant role in reducing the risk of relapse

• Promoted by donor lymphocyte infusions

Hurler syndrome

• Can be diagnosed at birth

• The deficiency results in the inability to digest sugar

Multiple Myeloma

• The defective plasma cells (myelomas) secrete M proteins, atypical antibodies that perform no beneficial function within the immune system → occupy precious space within the marrow → hindering production of healthy hematopoietic cells.

Acute Myeloid Leukemia (AML)

• Poor prognosis

• Overproduces immature WBCs (blasts)

• Allo transplant is the only curative treatment

Chronic Myeloid Leukemia (CML)

• Tyrosine kinase inhibitor (TKI) is the gold standard treatment

  • dasatinib

  • imatinib

  • nilotinib

• Allo transplant is the second line of treatment

What kind of disease is indicated for an auto transplant?

The disease is not rooted in the bone marrow itself.

Myelosuppresion

Decrease the ability of bone marrow transplant to produce RBCs, WBCs and platelets.

Myeloablation

The more severe form of myelosuppression

What kind of disease is indicated for an allo transplant?

• When the cause of the disease resides in bone marrow.

• Aggressive myeloablation treatments are used

Donor criteria for consideration

1. Blood type

2. Hx of blood transfusion

   • The more blood transfusion the donor gets, the more antibodies will develop

3. Gravidity

   • Fetus establishes its own blood supply and immune system in the womb→ woman’s immune system has been exposed to another immune system and develops antibodies for it.

   • Females have never been pregnant are preferred

4. Communicable disease

   • Viral hepatitis

   • HIV

5. Vaccination hx

   • Donor who is up to date on standard mandatory vaccinations should not be the first choice to donate stem cells to an individual who has never received those vaccines.

Which source of stem cells causes increased risk of long-term GVHD?

Peripheral blood stem cell

Which source of stem cells has:

• Extremely immature cells

• Decrease risk for posttransplant GVHD

• Finite number of available cells within the cord, which do not regenerate

• lack of quantity

• increased of opportunistic infection

• delayed engraftment

• Increased risk of failed transplant

Umbilical cord

Which cells intervene with allergic reactions?

Eosinophils

Which cells signal to others that a pathogen is present, and after elimination, allow for antibodies to be produced for future use with exposure

Neutrophils

Which drugs can be used to promote hydration of all cells in sickle cell disease?

Hydroxyurea

Penicillin VK

Thalassemia

Varrying types of anemia

Relying on multiple RBCs transfusion → iron overload → risk of organs failure

Myelodysplastic Syndrome

Bone marrow does not produce an adequate volume of platelets, RBCs or WBCs.

May convert to leukemia overtime

Need allo transplant

Haploidentical Allo Transplant

• Either from parents or from their children

• Challenging due to mismatched T cells → increase risk of GVHD

• Post Cytoxan to deplete those alloreactive T cells

Which kind of infection does not affect immune reconstitution following transplant?

Viral Infections

Advantages of Allo Transplant

• Disease-free stem cell source

• Potential for GVT effect = an immune response from do not T cells recognize and eliminating residual malignant host cells.

Donor Lymphocyte Infusion (DLI)

• Infusion from the original stem cell donor given in the setting of relapsed disease after an allo transplant

  • Use the immune system to fight the tumor by inducing a GVT effect

• Can induce risk of GVHD

• Patients with rapidly processing tumors will need chemotherapy before DLI to debunk tumor burden

• Can be used prophylactically for AML

Peripheral blood contains more ____ cells than bone marrow contains

T cells

• Increase risk of GVHD

Bone marrow harvests use the cells collected from the _________

Posterior iliac crest

• Take longer to engraft